“
“PURPOSE: To report refractive, topographic, aberrometric, GSK3326595 and tomographic outcomes 24 months after corneal cross-linking (CXL) in patients up to 18 years of age with progressive keratoconus.\n\nDESIGN: Prospective, interventional case series.\n\nMETHODS: Forty eyes underwent riboflavin-ultraviolet A-induced CXL. Uncorrected visual acuity (UCVA), best spectacle-corrected visual acuity (BSCVA), sphere and cylinder, topography, aberrometry, tomography, and endothelial cell counts were evaluated at baseline and at 1,

3, 6, 12, and 24 months.\n\nRESULTS: Mean logarithm of the minimum angle of resolution baseline UCVA and BSCVA were 0.79 +/- 0.21 and 0.39 +/- 0.10, respectively. Mean UCVA and BSCVA at 2 years were 0.58 +/- 0.18 and 0.20 +/- 0.09, respectively. The improvement in UCVA and BSCVA was significant throughout the postoperative follow-up (P < .05). Mean spherical equivalent refraction showed a significant decrease of 1.57 diopters (D) at 24 months (P = .02). Mean baseline simulated keratometry was 46.32 D in the flattest meridian and 51.48 D in the steepest meridian; at 2 years, the values were 45.30 D (P = .04) and 50.21 D (P = .07), respectively. For a 3-mm pupil, there was a significant reduction (P < .05) in whole

eye (total), corneal, higher-order, and astigmatic wavefront aberrations at 24 months. A significant difference (P < .05) in total coma and total spherical aberration Selleckchem VS-6063 2 years after CXL also was observed. Mean baseline pupil center pachymetry decreased significantly

(P = .04) at 6 Elafibranor Metabolism inhibitor months, but recovered by 12 months and remained stable thereafter through the 2-year follow-up. Endothelial cell counts did not change significantly (P = .32).\n\nCONCLUSIONS: CXL improved UCVA and BSCVA in the study patients, most likely by significantly reducing corneal asymmetry and corneal as well as total wavefront aberrations. (Am J Ophthalmol 2012;154:520-526. (C) 2012 by Elsevier Inc. All rights reserved.)”
“Background: Casts are well known components of the urinary sediment. For most casts, the clinical associations are known and demonstrated, while for waxy casts they are totally unknown.\n\nMethods: Prospective study for the search and count of waxy casts in the urinary sediment of patients with different types of glomerular diseases.\n\nResults: Waxy casts were found in 39 out of 287 patients (13.6%), mostly in low number (1 to 9 out of 100 casts evaluated/sample). They were frequent in postinfectious glomerulonephritis and renal amyloidosis (5/9 patients, 44.5%, p = 0.02 for each condition), while they were rare in membranous nephropathy (4/67 patients, 6.0%, 0.04) and absent in focal segmental glomerulosderosis (0/23 patients, p = 0.05). Waxy casts were associated significantly with higher serum creatinine levels (p < 0.

1% for drugs for which two clinical test LDN-193189 research buy cut-offs were available in both assays (didanosine,

abacavir, tenofovir, saquinavir/r, fosamprenavir/r, and lopinavir/r), from 2.4% to 8.1% for the drugs for which two clinical test cut-offs were available in the vT assay and one clinical test cut-off in the PS assay (lamivudine, stavudine, indinavir/r, and atazanavir/r) and from 3.1% to 10.3% for drugs for which biological test cut-offs were used (zidovudine, nevirapine, delavirdine, efavirenz, indinavir, ritonavir, nelfinavir, saquinavir, and fosamprenavir). Our analyses suggest that these assays provide comparable resistance information, which will be of value to physicians who may be presented with either or both types of test report in their practice. J. Med. Virol. 81: 1702-1709, 2009. (C) 2009 Wiley-Liss, Inc.”
“Viral glycoproteins mediate fusion between viral and cellular membranes upon binding to cognate receptors and/or experiencing low pH. Although activation of viral glycoproteins is thought to

be necessary and sufficient for fusion, accumulating evidence suggests that additional cellular factors, including lipids, can modulate the fusion process. Understanding the role of lipids in virus entry Nutlin-3a order via endocytosis is impeded by poor accessibility and the highly diverse nature of endosomes. Here we imaged fusion of single retroviral particles pseudotyped with the vesicular stomatitis virus (VSV) G protein with dextran-supported lipid bilayers. Incorporation of diffusible fluorescent labels into the

viral membrane and the viral interior enabled detection of the lipid mixing (hemifusion) and content PCI-34051 Epigenetics inhibitor transfer (full fusion) steps of VSV G-mediated fusion at low pH. Although single virus fusion with supported bilayers made of zwitterionic lipids could not be detected, inclusion of anionic lipids, phosphatidylserine, and bis(monoacylglycero) phosphate (BMP), greatly enhanced the efficiency of hemifusion and permitted full fusion. Importantly, lipid mixing always preceded the opening of a fusion pore, demonstrating that VSV G-mediated fusion proceeds through a long-lived hemifusion intermediate. Kinetic analysis of lipid and content transfer showed that the lags between lipid and content mixing defining the lifetime of a hemifusion intermediate were significantly shorter for BMP-containing compared with PS-containing bilayers. The strong fusion-enhancing effect of BMP, a late endosome-resident lipid, is consistent with the model that VSV initiates fusion in early endosomes but releases its core into the cytosol after reaching late endosomal compartments.”
“The present study was designed to investigate the potential of gadolinium, a stretch-activated calcium channel blocker in ischemic reperfusion (I/R)-induced brain injury in mice. Bilateral carotid artery occlusion of 12 min followed by reperfusion for 24 h was given to induce cerebral injury in male Swiss mice.

Higher photosynthetic efficiency was found in mats with a thinner and more densely populated euphotic zone. Microbial mats exhibit a lower https://www.selleckchem.com/products/acalabrutinib.html photosynthetic efficiency compared with ecosystems with a more open canopy-like organization of photosynthetic elements, where light propagation is not hindered to the same

extent by photosynthetically inactive components; such components contributed about 40-80% to light absorption in the investigated microbial mats, which is in a similar range as in oceanic planktonic systems.”
“A decline in estrogen levels during menopause is considered to be an important factor in the pathogenesis of Alzheimer’s disease (AD). Since neuroprotective effects of estrogens are mediated largely

through their cognate receptors, investigations of the expression of estrogen receptors (ER) in the human brain areas this website involved in the regulation of cognitive functions is of great importance. This mini-review summarizes the data obtained by the author on the ER expression in hippocampus, cholinergic basal forebrain nuclei, tuberomamillary and medial mamillary hypothalamic nuclei. The studies were carried out on postmortem brain material of men and women with AD and in control cases that were matched for age and gender. Immunocytochemical expression of the nuclear ER alpha in the basal forebrain and in the hypothalamus was markedly higher in AD patients than in control subjects. On the contrary, nuclear ER alpha in the hippocampus of AD patients was diminished. Using polymerase chain reaction, 62 ER alpha mRNA splice variants were isolated from different human brain areas. Fifty of them were found for the first time. The dominant negative variant Delta 7 (deletion of selleck chemicals exon 7) that can suppress estrogen signaling through classical ERs appeared to be the most common. The number of ER alpha mRNA splice variants detected per brain area

was more prominently decreased in AD women as compared to control. Moreover, the m RNA levels of the major ER alpha splice forms in the medial temporal cortex and in the hippocampus were notably diminished in AD women. Two novel ER alpha splice variants MB1 and TADDI were studied in detail at the protein level with the help of polyclonal antibodies. Immunocytochemical expression of TADDI was significantly elevated in the nucleus basalis of Meynert, tuberomamillary hypothalamic nucleus and in the hippocampus of postmenopausal women. In the same brain areas TADDI immunoreactivity was decreased in AD women. Taken together, the data show a clear tendency for the accumulation of the mutant forms of the ER alpha in the brain of postmenopausal women and for the down-regulation of the ER alpha mRNA alternative splicing in the brain of AD women.”
“Drug-resistant supraventricular tachycardia can cause hemodynamic instability, especially in infants.

Objective.-To evaluate changes in laboratory human papillomavirus (HPV) testing patterns in laboratories incorporating HPV testing with Papanicolaou tests in 2012. Design.-Data were analyzed from the CAP HPV Supplemental Questionnaire distributed to 1771 laboratories participating in either CAP HPV or CAP Papanicolaou proficiency testing in 2013. Results.-A total of 1022 laboratories (58%) responded. There were more high-risk (HR) HPV tests performed per institution as compared to previous surveys. There were more HPV tests performed within an

institution as compared to previous surveys. Hybrid Capture 2 (HC2) remains the most common method (42.4%, 239 Selleckchem 3-MA of 564); Cervista and cobas methods are used in 37.2% (210 of 564) and 14.9% (84 of 564) of laboratories, respectively. Human papillomavirus testing is offered as a reflex test after a Papanicolaou test result of atypical squamous cells of undetermined significance

(ASC-US) in 89.6% of laboratories (476 of 531); as a cotest for women aged 30 years and older in 60.3% (404 of 531); as reflex testing after atypical squamous cells, cannot see more exclude high-grade squamous intraepithelial lesion (ASC-H) in 42.7% (320 of 531); and as reflex testing after atypical glandular cells (AGC) in 27.3% (145 of 531). The HPV-positive rates for ASC-US and ASC-H were similar in 2012 and 2006. Cervista (49.2%, 88 of 179) and Roche cobas (27.4%, 49 of 179) are the most common methods used for genotyping. Most laboratories use the CAP Human Papillomavirus for Cytology Program for proficiency testing. Conclusions.-There was an increase in annual volume of HR-HPV testing with a shift toward in-house HR-HPV testing. Genotyping volumes also

increased. HC2 and Cervista are most commonly used, with an increasing volume of Roche cobas testing. The most common indication for HPV testing among all laboratories was ASC-US reflex testing, but an increase in HPV cotesting was observed. The data provide an update into persisting and newer trends in HPV testing practices.”
“Based on the structural similarity of viral fusion proteins within Selleck AZD1208 the family Paramyxoviridae, we tested recently described and newly synthesized acetanilide derivatives for their capacity to inhibit measles virus (MV)-, canine distemper virus (CDV)- and Nipah virus (NiV)-induced membrane fusion. We found that N-(3-cyanophenyl)-2-phenylacetamide (compound 1) has a high capacity to inhibit MV- and CDV-induced (IC(50)=3 mu M), but not NiV-induced, membrane fusion. This compound is of outstanding interest because it can be easily synthesized and its cytotoxicity is low [50% cytotoxic concentration (CC(50)) >= 300 mu M], leading to a CC(50)/IC(50) ratio of approximately 100. In addition, primary human peripheral blood lymphocytes and primary dog brain cell cultures (DBC) also tolerate high concentrations of compound 1.

“
“Objective: To obtain quantitative data on the progression of the most common spinocerebellar ataxias (SCAs) and identify factors that influence their progression, we initiated the EUROSCA natural history study, a multicentric longitudinal cohort study of 526 patients with SCA1, SCA2, SCA3, or SCA6. We report the results of the 1-and 2-year follow-up visits.\n\nMethods: As the primary outcome measure we used the Scale for www.selleckchem.com/products/wnt-c59-c59.html the Assessment and Rating of Ataxia (SARA, 0-40), and as a secondary measure the Inventory of Non-Ataxia Symptoms (INAS, 0-16) count.\n\nResults:

The annual increase of the SARA score was greatest in SCA1 (2.18 +/- 0.17, mean +/- SE) followed by SCA3 (1.61 +/- 0.12) and SCA2 (1.40 +/- 0.11). SARA progression in SCA6 was slowest and nonlinear (first year: 0.35 +/- 0.34, second year: 1.44 +/- 0.34). Analysis of the INAS count yielded similar results. Larger expanded repeats and earlier age at onset were associated with faster SARA progression in SCA1 and SCA2. In SCA1, repeat length of the expanded allele had a similar effect on INAS progression. In SCA3, SARA progression was influenced PKC412 in vitro by the disease duration

at inclusion, and INAS progression was faster in females.\n\nConclusions: Our study gives a comprehensive quantitative account of disease progression in SCA1, SCA2, SCA3, and SCA6 and identifies factors that specifically affect disease progression. Neurology (R) 2011; 77: 1035-1041″
“A newly developed mesoporous

mixed metal oxide (K-Cu-TiO2) catalyst is capable of highly selective, gas-phase benzyl alcoholbenzaldehyde transformation at excellent yields (>99%) under surprisingly low temperatures (203 degrees C, bp of benzyl alcohol). The tow-temperature reaction conditions and integration of K and Cu(I) components into the TiO2 matrix are of vital importance for the stabilization of an active Cu(I) oxidation state and resultant stable, excellent catalytic performance.”
“The accuracy of dynamical models for reactive scattering of molecular hydrogen, H(2), from metal surfaces is relevant to the validation of first principles electronic BLZ945 datasheet structure methods for molecules interacting with metal surfaces. The ability to validate such methods is important to progress in modeling heterogeneous catalysis. Here, we study vibrational excitation of H(2) on Cu(111) using the Born-Oppenheimer static surface model. The potential energy surface (PES) used was validated previously by calculations that reproduced experimental data on reaction and rotationally inelastic scattering in this system with chemical accuracy to within errors <= 1 kcal/mol approximate to 4.2 kJ/mol [D az C, et al. (2009) Science 326: 832-834]. Using the same PES and model, our dynamics calculations underestimate the contribution of vibrational excitation to previously measured time-of-flight spectra of H(2) scattered from Cu(111) by a factor 3.

This contrasts to delayed HT (> 18 to 24 hours after stroke) that relates to ischemia activation of brain proteases (MMP-2, MMP-3, MMP-9, and endogenous tissue plasminogen activator), neuroinflammation,

and factors that promote vascular remodeling (vascular endothelial growth factor and high-moblity-group-box-1). Processes that mediate BBB repair and reduce HT risk are discussed, including transforming growth factor beta signaling in monocytes, Src kinase signaling, MMP inhibitors, and inhibitors of reactive oxygen species. Finally, clinical features associated with HT in patients with stroke are reviewed, including approaches to predict HT by clinical factors, brain imaging, and blood biomarkers. Though remarkable advances in our understanding of HT have been made, additional efforts are needed to translate these discoveries to the clinic and reduce the impact of HT on patients with ischemic stroke.”
“A keratin click here degrading protease, Ker AP sharing peptide homology with putative

aminopeptidase RG-7388 from Pseudomonas aeruginosa was cloned and expressed as an extracellular protein using pEZZ18-Escherichia coli HB101. It was a serine hydrolase with pH and temperature optima of pH 10 and 60 degrees C. It had a t(1/2) of 20.50 min at 70 degrees C. It hydrolyzed various complex proteins such as fibrin, hemoglobin, feather and casein. Ker AP possessed fibrin(ogen)olytic activity along with plasminogen activating activity. In addition, it also cleaved tetra-peptides more efficiently than single amino acid pNA esters. In silico analysis was done to understand this endopeptidase character of this putative aminopeptidase. Domain mapping revealed that it had an additional protease associated domain along with the aminopeptidase domain. Modeling and docking studies revealed that

PA domain provided scaffold for binding of larger protein substrates facilitating its endopeptidase selleck compound character. Glu341, Ser423 and His296 were functionally validated to be probable catalytic triad for its endopeptidase activity. (c) 2013 Elsevier B.V. All rights reserved.”
“Laser-based photothermal therapies for urothelial cell carcinoma (UCC) are limited to thermal ablation of superficial tumors, as treatment of invasive lesions is hampered by shallow light penetration in bladder tissue at commonly used therapeutic wavelengths. This study evaluates the utilization of sharp, silica, fiberoptic microneedle devices (FMDs) to deliver single-walled carbon nanohorns (SWNHs) serving as exogenous chromophores in conjunction with a 1,064-nm laser to amplify thermal treatment doses in a spatially controlled manner. Experiments were conducted to determine the lateral and depth dispersal of SWNHs in aqueous solution (0.05 mg/mL) infused through FMDs into the wall of healthy, inflated, ex vivo porcine bladders.

The primary exposures analyzed were history of type II diabetes and diabetes medications. The primary outcomes were progression-free and overall ovarian cancer survival.\n\nRESULTS: Of the 341 ovarian cancer patients included in the study, 297 did not have diabetes, 28 were type II diabetic patients who did not use metformin, ACY-738 and 16 were type II diabetic patients who used metformin. The progression-free survival at 5 years was 51% for diabetic patients who used metformin compared with 23% for the nondiabetic patients and 8% for the diabetic patients who did not use metformin (P=.03). The overall survival

at 5 years was 63%, 37%, and 23% for the diabetic patients who used metformin, the nondiabetic patients, and the diabetic patients who did not use metformin, respectively (P=.03). The patients with diabetes received the same treatment for ovarian cancer as the patients without diabetes. The association of metformin use and increased progression-free survival, but not overall survival, remained significant after controlling for standard clinicopathologic parameters.\n\nCONCLUSION: In this ovarian cancer cohort, the patients with type II diabetes who used metformin had longer progression-free survival, despite receiving similar treatment for ovarian Autophagy phosphorylation cancer. (Obstet Gynecol 2012;119:61-7) DOI: 10.1097/AOG.0b013e3182393ab3″
“Seasonal

outbreaks of febrile illness with eschar have been occurring in Bishnupur district of Manipur since 2001. The aetiology of these outbreaks was unknown. We investigated a similar outbreak in 2007 in order to confirm the aetiology and identify its risk factors. We BV-6 molecular weight identified 38 patients who met the case definition (attack rate: 3.4/1000), including two deaths (case fatality ratio =

5.3%). Half of the female patients had eschar on the perineal area. The clinical picture and Weil-Felix positivity suggested that the outbreak was due to scrub typhus. The disease was more common among individuals who defecated or urinated in the jungle or bushy areas from a squatting position. We recommended educating the community about the common symptoms of the disease, encouraging them to seek early treatment from public health facilities and suggested that they be taught to avoid defecating/urinating from a squatting position in the jungle.”
“Background Six years ago, a survey of Australian trainees in neurology highlighted several differences in the training offered by the various positions. There has been a subsequent increase in trainee numbers. Aim This survey aimed to re-examine the workload and exposure provided by individual positions and to compare training in Australia and New Zealand. Methods A questionnaire was circulated in 2012 to all advanced trainees in core adult neurology positions in Australia and New Zealand, looking at ward work, outpatient clinics, neurophysiology exposure and on-call commitments. Results The response rate was 85.7%. There was a 48.

3 millions inhabitants) for the Epidemiology of Procedural Pain in Neonates ( EPIPPAIN) A-1210477 solubility dmso study.\n\nMain Outcome Measure Number of procedures considered painful or stressful by health personnel and corresponding analgesic therapy.\n\nResults The mean ( SD) gestational age and intensive care unit stay were 33.0 (

4.6) weeks and 8.4 ( 4.6) calendar days, respectively. Neonates experienced 60 969 first- attempt procedures, with 42 413 ( 69.6%) painful and 18 556 ( 30.4%) stressful procedures; 11 546 supplemental attempts were performed during procedures including 10 366 ( 89.8%) for painful and 1180 ( 10.2%) for stressful procedures. Each neonate experienced a median of 115 ( range, 4- 613) procedures during the study period and 16 ( range, 0- 62) procedures per day of hospitalization. Of these, BI 6727 price each neonate experienced a median of 75( range, 3- 364) painful procedures during the study period and 10 ( range, 0- 51) painful procedures per day of hospitalization. Of the 42 413

painful procedures, 2.1% were performed with pharmacological- only therapy; 18.2% with nonpharmacological- only interventions, 20.8% with pharmacological, nonpharmacological, or both types of therapy; and 79.2% without specific analgesia, and 34.2% were performed while the neonate was receiving concurrent analgesic or anesthetic infusions for other reasons. Prematurity, category of procedure, parental presence, surgery,

daytime, and day of procedure after the first day of admission were associated with greater use of specific preprocedural analgesia, whereas CCI-779 mechanical ventilation, noninvasive ventilation and administration of nonspecific concurrent analgesia were associated with lower use of specific preprocedural analgesia.\n\nConclusion During neonatal intensive care in the Paris region, large numbers of painful and stressful procedures were performed, the majority of which were not accompanied by analgesia.”
“The Pb atom in the polymeric title compound, [Pb(C13H9N3O2)]center dot CH3OH(n), is five-coordinated within an N2O2 donor set and a lone pair of electrons, as the N-isonicotinamidosalicylaldiminate ligand coordinates the Pb-II atom via the O,N,O’-donors and simultaneously bridges a neighbouring Pb atom via the pyridine N atom; the coordination geometry is based on a trigonal bipyramid with the O atoms in axial positions. The resulting supramolecular chain is a 3(1) helix along the c axis. These chains are linked via intermolecular Pb center dot center dot center dot O,N interactions, as well as O-H center dot center dot center dot O hydrogen bonds.”
“Introduction: Sub-therapeutic doses of antimicrobial agents are administered routinely to poultry to aid growth and to prevent disease, with prolonged exposure often resulting in bacterial resistance.

Although success can be expected in greater than 90% of these surgical patients, the optimal postoperative sedation management remains challenging.”
“An SIS epidemic model in two competing species with the mass action

incidence is formulated and analysed. Thresholds for the existence of boundary equilibria are identified and conditions for their local asymptotic stability or instability are found. By persistence theory, conditions for the persistence of either AZD1208 ic50 hosts or pathogens are proved. Using Hopf bifurcation theory and numerical simulations, some aspects of the complicated dynamic behaviours of the model are shown: the system may have zero up to three internal equilibria, may have a stable limit cycle, may have three stable attractors. Through the results on persistence and stability of the boundary equilibria, some important interactions Ispinesib between infection and competition are revealed: (1) a species that would become extinct without the infection, may persist in presence of the infection; (2) a species that would coexist with its competitor without the infection, is driven to extinction by the infection; (3) an infection that would die out in either species without the interinfection of disease, may persist in both species in presence of this factor. (C) 2007 Elsevier Ltd. All rights reserved.”
“Introduction:

This study aimed to compare hostility, impulsivity, and behavior inhibition between women with and without premenstrual dysphoric disorder (PMDD) during both luteal and follicular phases and to examine whether these variables contribute to irritability and daily functional impairment of PMDD.\n\nMethods: PMDD was screened via the Premenstrual Symptoms Screening Tool. A diagnosis of PMDD was confirmed by psychiatric interviewing without 2-month prospective confirmation. Sixty Sapitinib inhibitor women in the PMDD group and 60 women in the control group completed the Chinese Version of the Buss-Durkee Hostility Inventory-Short Form, Dickman’s Impulsivity

Inventory, and the Behavior Inhibition System Scale during the luteal and follicular phases.\n\nResults: We found that the PMDD group had significantly higher levels of hostility, dysfunctional impulsivity, and behavioral inhibition than the control group in both luteal and follicular phases. The PMDD group also had more premenstrual aggravation on total hostility, hostility affect, and suppressive hostility than the control group. Higher hostility, dysfunctional impulsivity, and behavior inhibition were associated with more severe irritability and functional impairment of PMDD.\n\nDiscussion: Hostility, impulsivity, and behavior inhibition might contribute to irritability and functional impairment in women with PMDD.\n\nConclusion: Assessment and interventions based on these factors should be provided for women with PMDD, especially in the luteal phase.

Some arguments are put forward HKI-272 in explanation of this phenomenon. Phenological studies have shown that airborne pollen results from both local and distant sources, although the pollen peaks usually appear when local sources are shedding the greatest amounts of pollen. Resuspension phenomena are probably more important than long-distance transport in explaining the presence of airborne pollen outside the flowering period. This information could be used to improve pollen forecasts.”
“Despite centuries of investigation, the function of the maxillary sinus (MS) and underlying patterns governing its form remain elusive. In this study,

we articulate a methodology for collecting volumetric data for the MS and nasal cavity (NC) from computed tomography (CT) scans and report details for a small sample of 39 dried human crania of known ecogeographic provenience useful for assessing variation in MS size

and shape. We use scaling analyses to preliminarily test the hypothesis that volumes selleck compound of the nasal cavity (NCV) and maxillary sinus (MSV) are inversely correlated such that the NC covaries with size of the face, whereas the MS “fills in” the leftover space [proposed by Shea: Am J Phys Anthropol 47 (1977), 289-300]. Against expectation, MSV is not significantly correlated with NCV or any cranial size variable. NCV, on the other hand, scales isometrically with facial size The results of this pilot study suggest that NCV covaries with facial size, but www.selleckchem.com/products/cx-4945-silmitasertib.html that the MS does not simply fill in the leftover space in the face. The role, if any, of the MSs in mid-facial function and architecture remains unclear. Larger sample sizes, additional environmental variables, and assessment of MS and NC shape are necessary to resolve this issue. Am J Phys Anthropol 143:426-436, 2010 (C) 2010 Wiley-Liss, Inc”
“Human

African trypanosomiasis (HAT, commonly known as African sleeping sickness) is categorized as a neglected disease, as it afflicts >50,000 people annually in sub-saharan Africa, and there are few formal programs in the world focused on drug discovery approaches for this disease. In this study, we examined the crude extracts of two fungal strains (Aspergillus fumigatus and Nectria inventa) isolated from deep water sediment which provided >99% growth inhibition at 1 mu g/mL of Trypanosoma brucei, the causative parasite of HAT. A collection of fifteen natural products was supplemented with six semi-synthetic derivatives and one commercially available compound. Twelve of the compounds, each containing a diketopiperazine core, showed excellent activity against T. brucei (IC(50) = 0.002-40 mu M), with selectivity over mammalian cells as great as 20-fold. The trypanocidal diketopiperazines were also tested against two cysteine protease targets Rhodesain and TbCatB, where five compounds showed inhibition activity at concentrations less than 20 mu M. A preliminary activity pattern is described and analyzed. (C) 2010 Elsevier Ltd. All rights reserved.